This grant is requested to support a program in basic research directed at elucidating at a molecular level the nature and mode of functioning of the smooth muscle alpha-adrenergic receptors for catecholamines. Catecholamines such as epinephrine and norepinephrine are of vital importance in the hormonal control of the entire circulation. These compounds regulate vascular tone via two distinct types of receptors termed alpha and beta. Alpha-Receptors cause vasoconstriction and Beta-receptors cause vasodilation. The specific aims of these studies include: 1) The development of radioligand binding techniques for studying alpha-adrenergic receptors in smooth muscle from peripheral vascular tissue. 2) The characterization in molecular terms of these alpha-adrenergic receptors. 3) The study of the factors which regulate the function of these receptors. These aims will be achieved by studying the binding of radioactively labeled alpha-adrenergic antagonists such as (3H)dihydroergokryptine to membrane fragments isolated from vascular and also uterine smooth muscle. Ultimately it should be possible to solubilize and purify the receptor binding proteins. Detailed characterization of these receptor structures will eventually permit evaluation of possible alterations in their structure and function in disease states such as hypertension.